# Role of sirtuin 6 in melanoma development and progression

> **NIH VA I01** · WM S. MIDDLETON MEMORIAL VETERANS HOSP · 2026 · —

## Abstract

Malignant melanoma is one of the deadliest forms of cancer among Veterans, and the existing therapeutic
options have not been fully effective in melanoma management, primarily owing to acquired drug resistance.
Therefore, novel target-based approaches are needed for the management of this neoplasm. The mammalian
sirtuins belong to a family of seven members (SIRT1 – SIRT7) with NAD+-dependent protein deacetylase
and/or ADP-ribosyltransferase activities, which play critical roles in important cellular processes, and are
involved in a variety of diseases, including cancer. We have an ongoing program to determine the roles and
functional significance of sirtuins in melanoma. Our published and preliminary data has shown a pro-
proliferative role of SIRT6 in melanoma in vitro and in vivo. Aberrant expression of SIRT6 has been shown to
enhance melanoma growth through an autophagy-dependent manner. Further, our ongoing active VA Merit
funding has provided compelling data suggesting that SIRT6 has a pro-proliferative role in melanoma and can
serve as a target for melanoma management via its small molecule inhibition. However, an understanding of
the mechanisms of the biological actions of SIRT6 in melanoma is far from complete. This may lead to the
identification of additional strategies for melanoma management. Further, NOTCH1 is a promising therapeutic
target, which is considered as a primary oncogenic factor in melanoma and linked with its metastasis. Thus,
development of efficacious novel inhibitors of SIRT6 and NOTCH1 is needed for potential future use against
melanoma (and other cancers). Interestingly, SIRT6 and NOTCH1 were found to be the target gene of the
micro-RNA (miR)-34a. Importantly, miR-34a is shown to be significantly downregulated in melanoma tissues.
However, the association of miR-34a with SIRT6 and NOTCH1 in melanoma is not known. Thus, based on
our published and preliminary data and available literature, we propose to test a hypothesis that miR-34a-
SIR

## Key facts

- **NIH application ID:** 11489894
- **Project number:** 5I01CX002210-06
- **Recipient organization:** WM S. MIDDLETON MEMORIAL VETERANS HOSP
- **Principal Investigator:** Nihal  Ahmad
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2026
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-10-01T00:00:00 → 2026-09-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11489894

## Citation

> US National Institutes of Health, RePORTER application 11489894, Role of sirtuin 6 in melanoma development and progression (5I01CX002210-06). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11489894. Licensed CC0.

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